Significance of Pelvic Fluid Observed during Ovarian Cancer Screening with Transvaginal Sonogram.

The primary objective was to examine the role of pelvic fluid observed during transvaginal ultrasonography (TVS) in identifying ovarian malignancy. A single-institution, observational study was conducted within the University of Kentucky Ovarian Cancer Screening trial from January 1987 to September 2019. We analyzed true-positive (TP), false-positive (FP), true-negative (TN), and false-negative (FN) groups for the presence of pelvic fluid during screening encounters. Measured outcomes were the presence and duration of fluid over successive screening encounters. Of the 48,925 women surveyed, 2001 (4.1%) had pelvic fluid present during a TVS exam. The odds ratio (OR) of detecting fluid in the comparison group (TN screen; OR = 1) significantly differed from that of the FP cases (benign pathology; OR: 13.4; 95% confidence interval (CI): 9.1-19.8), the TP cases with a low malignant potential (LMP; OR: 28; 95% CI: 26.5-29.5), TP ovarian cancer cases (OR: 50.4; 95% CI: 27.2-93.2), and FN ovarian cancer cases (OR: 59.3; 95% CI: 19.7-178.1). The mean duration that pelvic fluid was present for women with TN screens was 2.2 ± 0.05 encounters, lasting 38.7 ± 1.3 months. In an asymptomatic screening population, free fluid identified in TVS exams was more associated with ovarian malignancy than in the control group or benign ovarian tumors. While pelvic free fluid may not solely discriminate malignancy from non-malignancy, it appears to be clinically relevant and warrants thoughtful consideration.

Factors Predicting Participation in the Prospective Genomic Sequencing Study, Total Cancer Care (TCC), in Kentucky.

PURPOSE: Large-scale genomic sequencing studies are driving oncology drug development. However, rural populations, like those residing in Appalachian Kentucky, are underrepresented in these efforts. In this study, we determined the frequency of participation, reasons for nonparticipation, and factors predicting the decision to participate in the Total Cancer Care (TCC) prospective genomic cohort study. METHODS: A total of 1,188 patients were invited to enroll in the TCC prospective cohort from December 2018 to May 2019. Declining patients were queried for their rationale for nonparticipation and their patient data were obtained from the Kentucky Cancer Registry (KCR). Logistic regression was used to assess the association between characteristics and study participation. The association of study participation with survival was modeled with Cox proportional-hazards regression. RESULTS: 90.9% (1,081) patients consented to participate. In multivariate analysis, factors significantly associated with participation were age, gender, treatment status, and race. Though overall more women participated in the study, men were more likely to participate than women when invited (OR 1.57). Younger, Caucasian individuals who had received chemotherapy, but not surgery, were also more likely to participate. Patients in the Kentucky Appalachian cohort were primarily rural, had less educational attainment, and lower socioeconomic status. Kentucky Appalachian patients were no less likely to enroll in TCC than non-Appalachian patients. Consented individuals had higher overall survival compared to those who declined. CONCLUSION: Though minorities, those with low socioeconomic status, and rural populations are underrepresented in genomic studies, they were no less likely to participate when given the opportunity, and participation was associated with better clinical outcomes.

DACH1 mutation frequency in endometrial cancer is associated with high tumor mutation burden.

OBJECTIVE: DACH1 is a transcriptional repressor and tumor suppressor gene frequently mutated in melanoma, bladder, and prostate cancer. Loss of DACH1 expression is associated with poor prognostic features and reduced overall survival in uterine cancer. In this study, we utilized the Oncology Research Information Exchange Network (ORIEN) Avatar database to determine the frequency of DACH1 mutations in patients with endometrial cancer in our Kentucky population. METHODS: We obtained clinical and genomic data for 65 patients with endometrial cancer from the Markey Cancer Center (MCC). We examined the clinical attributes of the cancers by DACH1 status by comparing whole-exome sequencing (WES), RNA Sequencing (RNASeq), microsatellite instability (MSI), and tumor mutational burden (TMB). RESULTS: Kentucky women with endometrial cancer had an increased frequency of DACH1 mutations (12/65 patients, 18.5%) compared to The Cancer Genome Atlas (TCGA) endometrial cancer population (25/586 patients, 3.8%) with p-value = 1.04E-05. DACH1 mutations were associated with increased tumor mutation count in both TCGA (median 65 vs. 8972, p-value = 7.35E-09) and our Kentucky population (490 vs. 2160, p-value = 6.0E-04). DACH1 mutated patients have a higher tumor mutation burden compared to DACH1 wild-type (24 vs. 6.02, p-value = 4.29E-05). DACH1 mutations showed significant gene co-occurrence patterns with POLE, MLH1, and PMS2. DACH1 mutations were not associated with an increase in microsatellite instability at MCC (MSI-H) (p-value = 0.1342). CONCLUSIONS: DACH1 mutations are prevalent in Kentucky patients with endometrial cancer. These mutations are associated with high tumor mutational burden and co-occur with genome destabilizing gene mutations. These findings suggest DACH1 may be a candidate biomarker for future trials with immunotherapy, particularly in endometrial cancers.

Validation of an Endometrial Tumor Diameter Model for Risk Assessment in the Absence of Lymph Node Mapping.

PURPOSE: This study aimed to assess the optimal tumor diameter for predicting lymphatic metastasis and to determine intraoperatively the need for lymph node dissection in patients with endometrioid endometrial cancer. METHODS: Military beneficiaries diagnosed with stage I-III endometrioid endometrial cancer during 2003-2016 who had at least 7 pelvic and/or paraaortic lymph nodes removed during the time of hysterectomy were studied. Tumor diameter was compared against the presence of positive nodes, using the prior models of 20 mm (ie, Mayo model) and 50 mm (ie, Milwaukee model), to determine the false-negative rate of each threshold. A separate analysis was completed to determine the optimal diameter for our population. Receiver operating characteristic curve analysis models of tumor diameter were evaluated for model fit and predictive power of lymph node involvement. RESULTS: Of the 1224 patients with endometrioid endometrial cancer included, 13% (n=160) had positive lymph node involvement. Tumor sizes ranged from 1 mm to 100 mm. In contrast to Mayo and Milwaukee models (ie, Mayo, Milwaukee), the optimal tumor diameter independent of myometrial invasion and grade of tumor to predict lymph node metastasis was found to be 35 mm. CONCLUSIONS: Endometrioid endometrial cancer tumor diameter of 35 mm was found to be the optimal threshold for lymphadenectomy when the operating surgeon has no knowledge of tumor invasion.

Concurrent hysterectomy and bilateral salpingo-oophorectomy during cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for non-gynecologic cancers.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a key component of treatment in non-gynecologic peritoneal surface malignancies. As many as 10-15% of patients with a gastrointestinal primary malignancy will present with carcinomatosis. Maximal cytoreductive surgery directly affects the prognosis of patients. The routine inclusion of hysterectomy with bilateral salpingo-oophorectomy during these procedures optimizes cytoreduction despite negative pre-operative imaging and findings at the time of surgery. In this case series, we review twenty non-gynecologic cancer patients who underwent cytoreductive surgery with concurrent hysterectomy and bilateral salpingo-oophorectomy and HIPEC at our institution.

Hyperthermic Intraperitoneal Chemotherapy in Ovarian Cancer.

Hyperthermic intraperitoneal chemotherapy (HIPEC) in conjunction with cytoreductive surgery (CRS) holds promise as an adjunctive treatment strategy in malignancies affecting the peritoneal surface, effectively targeting remaining microscopic residual tumor. HIPEC increases concentrations of chemotherapy directly within the peritoneal cavity compared with the intravenous route and reduces the systemic side effects associated with prolonged adjuvant intraperitoneal exposure. Furthermore, hyperthermia increases tissue penetration and is synergistic with the therapeutic chemotherapy agents used. In ovarian cancer, evidence is building for its use in both primary and recurrent scenarios. In this review, we examine the history of HIPEC, the techniques used, and the available data guiding its use in primary and recurrent ovarian cancer.

The Eyes Do not Lie: A Case of Bilateral Subconjunctival Hemorrhages and Orbital Hematoma Postpartum.

Subconjunctival hemorrhages are common in trauma and with increased intra-abdominal pressure. Despite the sustained pressure endured while pushing, they are rarely observed postpartum and can be an indicator of underlying ophthalmic disease. We present a case of a postpartum patient who developed bilateral subconjunctival hemorrhages with a retro-orbital hematoma. The patient is a 29-year-old gravida-1-para-0 at 41 weeks gestation who underwent an uncomplicated induction and delivery. She developed diplopia and orbital pain postpartum. Imaging revealed an orbital hematoma with an ophthalmologic workup revealing suspected glaucoma. She was followed outpatient with symptomatic treatment and had resolution of symptoms after 4 weeks. This case demonstrates a rare postpartum scenario and the subsequent workup. Subconjunctival hemorrhages are rare in the postpartum period despite prolonged pushing efforts. Incorporating a multidisciplinary approach for diagnosis of a pregnant patient with ophthalmologic disease is required to optimize management in the antepartum, intrapartum, and postpartum periods.

Management of highly differentiated thyroid follicular carcinoma of ovarian origin with a minimally invasive approach.

•Peritoneal strumosis is highly differentiated thyroid follicular carcinoma of ovarian origin.•Minimally invasive surgical techniques for peritonectomy can resect extra-ovarian disease.•Multi-disciplinary collaboration allowed avoidance of thyroid ablation and thyroidectomy.